Thread by @fitterhappierAJ

I've been contacted by several people about someone using a review of T cell responses to sars cov 2 to claim that immunopathology and harm to T cells themselves does not exist. Simply put, the review is not exhaustive and is not focused on T cell dysregulation, that topic is beyond the scope of the review, and indeed, there are papers in a separate field of sorts that do cover this.

My specialization was T cell death and aging itself, and I posited and discovered a shared mechanism of death and differentiation in 2011.

I will address the claim of no harm to t cells here:

The claim that "COVID does not harm T cells" can be directly challenged by evidence from several studies.

These papers collectively demonstrate that SARS-CoV-2 infection, including its long-term manifestation as long COVID, induces specific and persistent damage to T cell populations and functionality in ways that distinguish it from typical viral effects.

First, a Nature Immunology study from January 2022 "Immunological dysfunction persists for 8 months following initial mild-to-moderate SARS-CoV-2 infection" shows that COVID-19 leads to a prolonged reduction in naive T cells (both CD4+ and CD8+) in individuals with long COVID, persisting up to eight months post-infection. Naive T cells are essential for initiating adaptive immune responses to new threats, and their depletion compromises the immune system’s ability to respond effectively over time. This sustained loss is accompanied by elevated interferon levels (IFN-β and IFN-λ1), suggesting a chronic inflammatory state that disrupts T cell homeostasis. Such a long-term impact on the naive T cell pool is not a standard feature of recovery from other acute viral infections like influenza, directly contradicting the assertion that COVID-19 does not harm T cells. The paper states it was unique to covid and compares it to other viral infections. This effect may not completely persist, however, what it represents is sloughing of the T cells.

Second, the Immunity study "Robust T cell responses to the Pfizer/BioNTech vaccine compared to infection and evidence of attenuated CD8+ T cell responses due to COVID-19" provides evidence of specific harm to CD8+ T cells, the cytotoxic T cells critical for killing virus-infected cells. The study found that unvaccinated individuals with prior SARS-CoV-2 infection exhibited significantly reduced levels of spike-specific CD8+ T cells compared to vaccinated individuals without prior infection. Even after vaccination, those with a history of COVID-19 showed weaker and less functional CD8+ T cell responses, a phenomenon likened to the immune damage seen in chronic viral infections like hepatitis C or HIV. This attenuation indicates that SARS-CoV-2 inflicts a lasting impairment on CD8+ T cell effector function, undermining the claim that T cells remain unharmed by COVID-19.

Thirdly, there is a paper in JCI insight showing T cell exhaustion to other infections following a covid infection. It is often overlooked by naysayers. insight.jci.org/articles/view/…

Finally, a Nature Immunology study from January 2024 "Long COVID manifests with T cell dysregulation, inflammation and an uncoordinated adaptive immune response to SARS-CoV-2" reveals further harm through T cell dysregulation in long COVID patients. The research identified increased frequencies of exhausted SARS-CoV-2-specific CD8+ T cells, alongside CD4+ T cells primed for inflammation, and a lack of coordination between T and B cell responses. T cell exhaustion—where T cells lose their ability to effectively respond to antigens—is a hallmark of immune dysfunction and was notably absent in individuals who fully recovered from COVID-19 without long-term symptoms. This chronic exhaustion and misalignment of the adaptive immune response highlight a specific deleterious effect of SARS-CoV-2 on T cells, refuting the idea that COVID-19 leaves them unscathed.

Together, these studies demonstrate that COVID-19 harms T cells in multiple ways: it depletes naive T cells, impairs CD8+ T cell functionality, and drives chronic exhaustion and dysregulation, particularly in long COVID. These effects persist beyond the acute phase of infection and differ from the transient T cell changes seen with many other virusescontrary to the claim that "COVID does not harm T cells."